distinguished expression pattern of metastasis was shown in our clinical cohort. AKR1B10 was dramatically overexpressed in PDAC tumor spheres. AKR1B10 knock in and knock out caused a potential impact on cell metabolic plasticity via autophagy. Overexpression or administration of recombinant protein of AKR1B10 enriches the cancer stem cells with upregulated expression of metastasis associated genes (such as Osteo- pontin, CXCR4 and MMPs). Co-culture of pancreatic stellate cells promote PDAC AKR1B10 expression. Genetical or pharmacological downregulation of AKR1B10 decrease the stem like subpopulation of PDAC and inhibit PDAC progression. Conclusion: Our study demonstrates a remarkable impact of AKRB10 on the biology of PDAC. Overexpression of AKR1B10 in PDAC tumor sam- ples may indicate resistance to gemcitabine based adjuvant therapy. Tar- geting AKR1B10 dysregulated cancer stem cells and the niche may restore sensitivity to gemcitabine treatment and reverse EMT process which will be able to reduce metastasis. P4-25. Pancreatic stellate cell-derived citrate switches pancreatic cancer cell metabolism towards a more mitochondrial phenotype with minimal effects on bioenergetics and cytosolic Ca2+ homeostasis Jason I.E. Bruce 1 , Ahlam Sultan 1 , Andrew James 2 , Daniel A. Richardson 1 , Howbeer Muhamad-Ali 3 , Royston Goodacre 3 1 University of Manchester, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester, United Kingdom 2 University of York, Division of Cancer Sciences, Department of Biology, Heslington, York, YO10 5DD, United Kingdom 3 University of Liverpool, Institute of Integrative Biology, Faculty of Health and Life Sciences, Brownlow Hill, Liverpool, L69 3BX, United Kingdom Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) has poor survival and limited treatment options, due in part to the dense tumour microenvironment (pancreatic stellate cells (PDCs) and matrix), which reduces blood flow and thus drug delivery. PDAC cells undergo a switch from mitochondrial to glycolytic metabolism (Warburg effect) which facilitates numerous cancer hallmarks. Our previous studies show that inhibiting glycolytic ATP supply to the plasma membrane cal- cium pump (PMCA) causes cytotoxic Ca 2+ overload and cell death. Previous studies show that PSCs release key metabolites (e.g. alanine) that drive a more mitochondrial phenotype in PDAC. We aim to investigate the effect of PSC conditioned media (and PDAC-PSC co-culture) on the metabolic phenotype in relation to cytosolic Ca 2+ homeostasis in PDAC cells. Materials and Methods: Human PDAC cells (Mia PaCa-2) and PSCs (hPSCs) were cultured in standard DMEM and conditioned media was collected at 24-72 hours. Glycolysis and mitochondrial respiration was assessed using the Seahorse XFe96 analyzer. Cellular ATP was assessed using a luciferase-based luminescence assay. Fura-2 imaging was used to asses cytosolic Ca 2+ [Ca 2+ ] i . Metabolomics of conditioned media was per- formed using gas chromatography mass spectrometry (GC-MS). Results: Conditioned media from hPSCs increased PDAC cell mito- chondrial metabolism and reduced glycolysis, independent of glucose depletion or lactate accumulation. Metabolomics identified citrate as the only metabolite elevated in hPSC but not PDAC conditioned media. Sup- plementing DMEM with citrate (1-10 mM) increased mitochondrial metabolism (1mM) and decreased glycolysis (10mM). However, PDAC cells in co-culture with hPSCs exhibited a similar sensitivity to metabolic in- hibitor-induced ATP depletion and cytosolic Ca 2+ overload, compared to singly cultured PDAC cells. Conclusion: PSC-derived citrate drives PDAC cell mitochondrial metabolism that is likely important for biosynthesis (fatty acid meta- bolism) and thus tumour growth, rather than bioenergetics. This suggests that cutting off the glycolytic ATP supply to the PMCA in PDAC cells within the tumour microenvironment remains a valid and realistic therapeutic strategy. P4-26. Periampullary gangliocytic paraganglioma Yi-Ming Shyr Taipei Veterans General Hospital, General Surgery, Taipei, Taiwan Background and Objectives: Gangliocytic paraganglioma (GP) is rare and difficult to be differentiated from other periampullary neoplasms. The clinical characteristics and optimal treatment of periampullary GPs have not been clarified. Materials and Methods: The data pool for the analysis comprised of cases of periampullary GP encountered in our institution and sporadic cases reported in the English literature. Results: A total of 117 cases with periampullary GP were studied, including 2 from our institute, and among them, duodenal GP was the most common (53.0%). GP size ranged from 0.7 cm to 19.0 cm, with a median of 2.2 cm. The most common presenting symptom for overall periampullary GPs was epigastric pain in 49.5% cases, followed by gastrointestinal bleeding in 35.4% cases. Most (84.1%) of the periampullary GPs were benign, whereas 15.9% were malignant. Metastasis was noted in 26.3% of periampullary GPs, with 14.5% showing lymph node metastasis and 1.8% showing liver metastasis. Of the periampullary GP cases included, 30.1% were treated with pancreaticoduodenectomy, 40.6% with local excision, and 17.7% with endoscopic resection. Conclusion: Periampullary GP should be considered as a tumor with malignant potential. Endoscopic resection is the treatment of choice for most of the duodenal GPs, whereas pancreaticoduodenectomy is recom- mended for GPs with possible malignancy, such as large size, with sub- mucosal invasion, or pancreatic GP. P4-27. Hepatoid carcinoma of the pancreas Yi-Ming Shyr, Shin-E. Wang Taipei Veterans General Hospital, General Surgery, Taipei, Taiwan Background and Objectives: Hepatoid carcinoma of the pancreas is extremely rare. This study tried to clarify the clinical features and outcome of pancreatic hepatoid carcinoma. Materials and Methods: The data pool for the analysis was collected from the case with hepatoid carcinoma of the pancreas encountered by our institution and sporadic cases reported in the English literature. Results: A total of 23 cases of hepatoid carcinoma of the pancreas were collected for study. This tumor occurred more frequently in male patients than in female (69.6% vs. 30.45%). The median tumor size was 6.0cm (0.5 ~ 11.0 cm). For overall patients, the most common symptom was epigastric pain (36.4%). For pancreatic head group, the most common symptom was nausea/vomiting (62.5%), followed by jaundice and epigastric pain (50.0%). For pancreatic body-tail group, 42.9% presented no symptom, and 28.6% epigastric pain. Hepatoid carcinoma in the pancreas could be either pure form or mixed (40.9%) with other pathology. The most common co-exited pathology was malignant neuroendocrine tumor (22.7%). Overall, metas- tasis occurred in 36.4% cases at the diagnosis of this tumor, including liver metastasis in 31.8% and lymph node metastasis in 21.1%. The overall 1-year survival rate was 71.1% and 5-year 40.4%, with a median of 13.0 months and a mean of 18.1+21.8 months. Metastasis, either liver or lymph node metastasis, was associated with negative impact on survival outcome. Prognosis in tumor resection group was significantly better than non- resection group. Conclusion: Elevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma; however, diagnosis is usually made based on specific histological findings after resection. This tumor could be mixed with other more common pancreatic tumors, such as neuroendocrine tumors. Surgical resection should be the treatment of choice whenever possible. Abstracts / Pancreatology 19 (2019) S1eS180 S84